Secukinumab 2-weekly vs. 4-weekly Dosing in Patients With Plaque-type Psoriasis

Results From the Randomized GAIN Study

K. Reich; A. Körber; U. Mrowietz; M. Sticherling; C. Sieder; J. Früh; T. Bachhuber

Disclosures

The British Journal of Dermatology. 2021;184(5):849-856. 

In This Article

Abstract and Introduction

Abstract

Background: Secukinumab is a fully human monoclonal antibody that selectively neutralizes interleukin-17A and shows long-lasting efficacy and safety in plaque psoriasis. More evidence is required to optimize secukinumab dosing according to clinical response.

Objectives: GAIN compared the efficacy and safety of secukinumab 300 mg every 2 weeks (q2w) with 300 mg every 4 weeks (q4w) in patients achieving ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75) but not PASI 90 after 16 weeks.

Methods: In total, 772 patients with moderate-to-severe plaque psoriasis received secukinumab 300 mg subcutaneously at baseline and weeks 1, 2, 3 and 4, then q4w until week 16. At week 16, patients with PASI ≥ 75 to PASI < 90 were randomized 1: 1 to continue q4w dosing (n = 162) or switch to q2w (n = 163) to week 32. The primary endpoint was superiority of q2w to q4w dosing for PASI 90 response at week 32.

Results: PASI 90 response at week 32 was numerically greater with secukinumab 300 mg q2w than with secukinumab 300 mg q4w in suboptimal responders, but this did not reach statistical significance (64·4% vs. 57·4%; odds ratio 0·64, 95% confidence interval 0·39–1·07; P = 0·087). Although the primary endpoint was not met, absolute PASI was significantly lower at week 32 in q2w vs. q4w patients (2·11 vs. 2·84, P = 0·024). Significantly more patients with q2w vs. q4w dosing showed minimal disease activity (Investigator's Global Assessment score 0 or 1: 73·0% vs. 64·1%, P < 0·05) and improved quality of life (Dermatology Life Quality Index score 0 or 1: 58·9% vs. 50·6%, P < 0·05) at week 32. No new or unexpected safety signals arose.

Conclusions: Most patients achieved PASI 90 response with secukinumab q4w. There was potential benefit of q2w dosing in some suboptimal responders. Continued q4w treatment can improve response even after 16 weeks.

Introduction

Psoriasis is a chronic inflammatory condition in which treatment strategies for long-term management and the achievement and maintenance of optimal response are essential. Psoriasis Area and Severity Index (PASI) score is used clinically to assess disease severity and response to treatment. A reduction in PASI score by ≥ 75% (PASI 75) by week 16 of treatment was typically regarded by consensus as the established treatment target for psoriasis therapies.[1,2] However, with the advent of newer biologic treatments including anti-interleukin (IL)-17A agents, PASI 90, representing clear or almost clear skin, has become the accepted clinically realistic treatment standard.[3,4] PASI 90 was shown to increase significantly the likelihood of patients reporting a Dermatology Life Quality Index (DLQI) score of 0 or 1, indicating no to minimal impact of psoriasis on quality of life.[5]

Secukinumab is a fully human monoclonal antibody that selectively neutralizes IL-17A, the key cytokine involved in the development of psoriasis.[6] Secukinumab has shown long-lasting efficacy and safety in a wide spectrum of psoriasis manifestations, including nails, scalp, palms and soles, and psoriatic arthritis.[7–10]

The majority of patients treated with the label dose of secukinumab 300 mg achieve PASI 90 at week 16 of treatment.[7,11,12] A subset of patients achieve PASI 75 after 16 weeks of treatment, but do not reach PASI 90. However, psoriasis is also associated with flares as part of the natural course of the disease, and therefore it is important to determine that these are not mistaken for a loss of response. Dose adjustments of biologic treatments may occur in clinical practice,[13] but systematic evidence for increased or individualized dosing of secukinumab in suboptimal responders is lacking. The GAIN study was designed to compare the efficacy and safety of increasing the dose of secukinumab to 300 mg every 2 weeks (q2w) against the approved dose of 300 mg every 4 weeks (q4w) in patients achieving PASI 75 but not PASI 90 after 16 weeks of initial treatment.

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